03-cs01-intro

Author
Affiliation

Professor Shannon Ellis

UC San Diego
COGS 137 - Fall 2024

Published

October 3, 2023

CS01: Biomarkers of Recent Use (Data)

Q&A

Coming Soon

Q:
A:

Course Announcements

Coming Soon

Agenda

  • Background
  • Data Intro
  • Paper Results
  • Wrangle

Background

Case Studies in COGS 137

  • Question + Data Provided
  • Wrangling + Analysis Discussed/Presented in Class
  • In groups:
    • reproduce the analysis
    • extend the analysis

Deliverables

  • Full Rmd report (explanations, text and story matter!)
  • General Audience communication

CS01: Biomarkers of Recent Use

  • Focuses on Data Wrangling and EDA
  • Uses real research data from a collaboration w/ Rob Fitgerald’s group

Motor Vehicle Accidents (MVAs)

  • 2/3 of US trauma center admissions are due to MVAs
  • ~60% of such patients testing positive for drugs or alcohol
  • Alcohol and cannabis are most frequently detected

Source: https://academic.oup.com/clinchem/article/59/3/478/5621997

Legalization of Marijuana

  • Federally illegal in the US
  • Decriminalized in many states
  • Medically available in 15 states
  • Legal for recreational use in 24 states (including CA)

Increased roadside surveys

  • 25% increase in use nationwide from 2002 to 2015 (survey)
  • THC detection in drivers increased by 48% from 2007 to 2014
  • Increased prevalence of consumption -> possible intoxication -> possible impaired driving -> public health concern

DUI of Alcohol (DUIA)

  • The science is there. Don’t do it.
  • DUIA has decreased since the 1970s
    • % of nighttime, weekend drivers testing over the legal limit (BAC > 0.08 g/dL) decreased from 7.5% (1973) to 2.2% (2007) link

DUI of Cannabis

  • In a 2007 survey, 16.3% of nighttime drivers were drug-positive link
    • 8.6% of these tested positive for THC
  • Experimental and cognitive studies suggest cannabis-induced impairment increases risk of motor vehicle crashes:

. . .

Evidence suggests recent smoking and/or blood THC concentrations 2–5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers.link

Roadside Detection

  • per se laws: “a driver is deemed to have committed an offense if THC is detected at or above a pre-determined cutoff” link

. . .

  • Defining cutoffs for safe driving is difficult
  • THC concentration differs by:
    • “smoking topography” (time to smoke; number of puffs)
    • frequency of use
    • route of ingestion

. . .

As of 2021…link

  • 19 states have per se or zero tolerance cannabis laws
  • States with per se laws (Illinois, Montana, Nevada, Ohio, Pennsylvania, Washington and West Virginia), cutoffs range from 1 to 5 ng/mL THC in whole blood.
  • In 3 states, per se limits also apply to THC metabolites
  • Colorado: “reasonable inference” - blood contained >5 ng/mL THC at the time of the offense
  • 3 states zero tolerance for THC; 8 states for THC and metabolites

Metabolism

  • peak blood concentrations occur during smoking, then drop rapidly link
  • subjective ‘high’ persists for several hours, varies greatly between individuals
  • THC concentrations remain detectable in frequent users longer than occasional users link
  • THC and certain metabolites can be detected in blood for weeks to months after use and do not necessarily indicate impairment

Detection

Various approaches:

  1. Detect impairment (officers detect DUIC)
  2. Detect recent use (test for compounds)
  3. Combine recent use + impairment

. . .

Focus here: Can we identify a biomarker of recent use?

  • recent use: defined here as within 3h
  • testing THC and metabolites in blood, oral fluid (OF), and breath

Aside: Case Study Report

  • Your Case study will need a background section
  • It can use/summarize/paraphrase the information here (you should cite the source, not me)
  • But, you’re not limited to this information
  • You are allowed/encouraged to dig deeper, include what’s most important, add to, remove, etc.
  • There are a lot of citations in this section - go ahead and peruse them/others/use references in these papers

Question

Which compound, in which matrix, and at what cutoff is the best biomarker of recent use?

The Data

Participants

  • placebo-controlled, double-blinded, randomized study

. . .

  • recruited:
    • volunteers 21-55 y/o
    • had a driver’s license
    • self-reported cannabis use >= 4x in the past month

. . .

  • Participants were:
    • compensated
    • medically evaluated (for safety)
    • asked to refrain from use for 2d prior to participation
    • exclusion criteria: OF THC concentration ≥5 ng/mL on day of study (n=7)

. . .

  • Study included 191 participants

Demographics

Source: Hoffman et al.

Experimental Design

Participants were:

  • randomly assigned to receive a cigarette containing placebo (0.02%), or 5.9% or 13.4% THC
  • Blood, OF and breath were collected prior to smoking
  • smoked a 700 mg cigarette ad libitum within 10 min, with a minimum of four puffs.
  • After smoking, 4 additional OF and breath and 8 blood collections were completed at time points up to ∼6h from the start of smoking.
  • Participants ate and drank water between collections, although not within 10 min of OF collection.

Timeline

Source: Fitzgerald et al.

Consumption

Source: Hoffman et al.

Topography

Source: Hoffman et al.

Subjective Highness

Source: Hoffman et al.

Our Datasets

Three matrices:

  • Blood (WB): 8 compounds; 190 participants
  • Oral Fluid (OF): 7 compounds; 192 participants
  • Breath (BR): 1 compound; 191 participants

. . .

Variables:

  • ID | participants identifier
  • Treatment | placebo, 5.90%, 13.40%
  • Group | Occasional user, Frequent user
  • Timepoint | indicator of which point in the timeline participant’s collection occurred
  • time.from.start | number of minutes from consumption
  • & measurements for individual compounds

The Data

You’ll have access once your groups/repos are created…(today I want people to follow along; there will be time to try on your own soon!)

WB <- read_csv("data/Blood.csv")
BR <- read_csv("data/Breath.csv")
OF <- read_csv("data/OF.csv")

First Look at the data (WB)

First Look at the data (OF)

First Look at the data (BR)

Analysis

Where We’re Headed…

Results from: Hubbard et al (2021) Biomarkers of Recent Cannabis Use in Blood, Oral Fluid and Breath link

Fig 1: Pre-smoking

Fig 2: Sensitivity and Specificity

Fig 3: Cross-compound relationship

Fig 4: Cutoffs

Fig 5: Youden

. . .

…and if there’s time PPV and Accuracy post 3h

What Came After

Source: Fiztgerald et al.

Recap

  • Could you summarize/explain background presented?
  • Could you summarize the experiment that was done?
  • Could you describe the datasets? (variables, observations, values, etc.)